Antivenom administration for North American Crotalinae snakebites (rattlesnakes, water moccasins, and copperheads)

Consultation with a medical toxicologist or other physician with expertise and prior experience treating venomous snake bites is strongly encouraged before initiating antivenom therapy for bites by Crotalinae snakes found in North America (rattlesnakes, water moccasins [cottonmouths], and copperheads). Emergency consultation with a medical toxicologist in the United States is available at 1-800-222-1222.
	Antivenom
	Crotalidae immune equine F(ab')2 (Fab2AV, Anavip)	Polyvalent Crotalinae ovine immune Fab (FabAV, CroFab)
Initial dose*	10 vials; repeat dose if initial control of local and systemic venom effects not achieved Call physician expert if initial control not achieved after 2 loading doses^¶	4 to 6 vials; repeat dose if initial control of local and systemic venom effects not achieved 8 to 12 vials if patient in shock or with serious active bleeding Call physician expert if initial control not achieved after 2 loading doses^¶
Maintenance doses?	No: Patient should be observed for an additional 18 hours after control achieved	Yes: 2 vials every 6 hours for 3 doses
As-needed doses for recurrent venom effects	4 vials	2 vials
Timeline for reassessment of platelets and fibrinogen	5 to 7 days after last antivenom dose; continue to monitor if trend toward abnormal Reassess sooner if risks for bleeding present Patients who received both FabAV and Fab2AV: 2 to 3 days and 5 to 7 days after last antivenom dose; continue to monitor if trend toward abnormal	2 to 3 days and 5 to 7 days after last antivenom dose; continue to monitor if trend toward abnormal Reassess sooner if risks for bleeding present Patients who received both FabAV and Fab2AV: 2 to 3 days and 5 to 7 days after last antivenom dose; continue to monitor if trend toward abnormal

Indications for antivenom treatment of Crotalinae envenomation include swelling that extends beyond the bite site or is progressing; face or neck bites with any swelling; hemotoxicity (thrombocytopenia, hypofibrinogenemia, or prolonged prothrombin time [PT]); or other systemic toxicity such as bleeding, shock, myokymia (rippling muscle movement of the face and extremities), and/or, rarely, weakness/paralysis after bites by Mohave or Southern Pacific rattlesnakes. Coagulation testing should include complete blood count with a focus on the platelet count, PT, international normalized ratio (INR), and plasma fibrinogen at patient presentation. At 4 hours or longer after the bite, some experts also obtain fibrin degradation testing, either D-dimer or fibrin split products, to identify patients whose initial studies do not show significant abnormalities but who remain at risk for delayed hemotoxicity. Antivenom therapy does not affect the results of fibrin degradation tests. For more details, refer to UpToDate content on use of antivenom to manage North American Crotalinae snakebite.

Antivenom administration is associated with potentially severe allergic reactions; it should only occur in a continuously monitored emergency or intensive care unit setting. During administration, the physician should ensure the immediate availability of epinephrine ([concentration 1 mg/mL] 0.3 to 0.5 mg intramuscularly in the anterolateral thigh, [concentration 0.1 mg/mL] prepared for continuous intravenous infusion), diphenhydramine or similar antihistamine, intravenous corticosteroids, and inhaled albuterol.

* Dose is the same for children and adults. Reconstitution depends upon the antivenom used:

Fab2AV (Anavip) – Reconstitute each vial of lyophilized power with 10 mL of sterile normal saline and mix with continuous, gentle swirling. Typical reconstitution time is less than 1 minute per vial. The resultant material is yellow/green and opalescent.
FabAV (CroFab) – The manufacturer suggests the modified method for reconstitution: Inject 18 mL sterile normal saline into the vial and manually invert about 2 times per second (do not shake) until completely dissolved by visual inspection. The resulting antivenom should appear weakly yellow and opalescent. Typical reconstitution time is 3 minutes.

For both antivenoms, do not use if otherwise discolored or turbid.

Once either FabAV or Fab2AV is reconstituted, combine contents of all vials and further dilute to a total of 250 mL sterile normal saline. Infuse within 4 hours of preparation; administer the antivenom as an intravenous infusion at an initial rate of 25 to 50 mL/hour for the first 10 minutes. If tolerated, increase the rate to finish the infusion over 1 hour. If signs of adverse effects (eg, urticaria, lip or tongue swelling, difficulty breathing, or hypotension) develop, immediately stop the infusion. Refer to UpToDate content on treatment of acute reactions caused by North American Crotalinae snake antivenom for further recommendations.

¶ Control of envenomation is achieved when all of the following are present:

Hemodynamic stability
Improvement in other systemic findings such as vomiting, diarrhea, or altered mental status
Lack of progression of tissue swelling adjacent to the bite site
Partial or complete reversal of hematologic toxicity based upon repeated laboratory studies performed one hour after each dose of antivenom; studies should include a complete blood count, prothrombin time (PT), international normalized ratio (INR), and fibrinogen

References:

Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: Results of an evidence-informed consensus workshop. BMC Emerg Med 2011; 11:2.
Bush SP, Ruha AM, Seifert SA, et al. Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial. Clin Toxicol (Phila) 2015; 53:37.
Highlights of prescribing information. ANAVIP. Crotalidae Immune F(ab')2 (Equine). Available at: https://www.fda.gov/media/92139/download (Accessed on June 10, 2019).
CroFab: Dosing and administration. Available at: https://crofab.com/treating-with-crofab/dosing (Accessed December 22, 2021).
Gerring D, King TR, Branton R. Validating a faster method for reconstitution of Crotalidae Polyvalent Immune Fab (ovine). Toxicon 2013; 69:42.

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Antivenom administration for North American Crotalinae snakebites (rattlesnakes, water moccasins, and copperheads)